Human immunodeficiency virus type 1 (HIV-1) infects the central nervous system of adults and children. Little is known about HIV-1 infection of the fetal nervous system, or about the indirect effects of maternal HIV-1 infection on the developing fetal brain. The marked host species specificity of lentiviruses and the importance of viral-host cell interactions suggest that a model is required in which intact, differentiating, fetal neural tissue can be infected by HIV-1 and/or exposed to potentially toxic viral or host derived factors. We have developed a model in which human second trimester fetal brain or retinal tissues are grown as xenografts in the anterior chamber of the eye in adult rats. These xenografts vascularize, establish a blood-brain-barrier, and partially differentiate into glial and neuronal elements. We propose to establish and optimize conditions for infecting these human fetal neural tissues with HIV-1. To analyze the course of the HIV-1 infection, we will use polymerase chain reaction (PCR), coupled with immunohistochemical and in situ hybridization techniques. Additional studies will allow us to determine which viral strains of HIV-1 are capable of infecting human fetal brain, which cell types (neuroectodermal or other) are infected, the nature of infection in each cell type (productive, restricted, or latent), and the morphological effects, direct or indirect, of HIV-1 on the developing nervous system. This model should prove useful in assessing the efficacy of antiviral agents which target HIV-1 infection of the nervous system.